S. typhimurium is the most common cause of foodborne illness with lethal outcome in the US. The ability of S. typhimurium to consistently contaminate our food supply, creates an urgent need for better understanding of the molecular mechanisms that allow this pathogen to persist successfully in food producing animals. Epidemiological surveillance strongly suggests that pigeon adapted S. typhimurium variants (phage types DT2 and DT99) that cause fatal pigeon paratyphoid do not persist in cattle. The objective of this proposal is to identify the genes responsible for the epidemiologic success of S. typhimurium.in cattle through genomic comparison and characterize their function using the calf model of enterocolitis. The first specific aim of this proposal is to evaluate the virulence and persistence of S. typhimurium pigeon adapted variants in calves. The calf ligated ileal loop model will be used to evaluate the ability of pigeon variants to cause fluid accumulation, inflammation and tissue damage in the calf small intestine, and persistence in calves will be studied using oral models of infection. The second specific aim of this proposal is to identify genes present in S. typhimurium strain LT2 but absent from pigeon isolates. To identify LT2 specific genes unique to cattle isolates we will establish a epidemiological correlation within a large number of S.typhimurium isolates by southern blotting. The final specific aim of this proposal is to test unique regions of DNA isolated from S. typhimurium cattle variants for the ability to alter host specificity of pigeon adapted S. typhimurium isolates. Dr. Andrews-Polymenis completed her Ph.D. in the laboratory of Dr. Ralph Isberg, identifying novel factors necessary for intracellular growth of Legionella pneumophila. She completed her D.V.M. cum laude at Texas A&M University College of Veterinary Medicine in May 2001. Having a strong interest in bacterial pathogenesis and in veterinary medicine, Dr. Andrews-Polymenis' career goal is to become an independent investigator at the interface between these two areas. The research collaboration between Dr. Baumler in the Texas A&M Health Science Center and Dr. Adams in the College of Veterinary Medicine provides a unique opportunity to achieve this career goal.